Variational quantum algorithms are a leading approach to near-term quantum computing, but their scalability can be limited by barren plateaus and the sampling cost of resolving small changes in the loss landscape. Here, we study the trainability of passive linear-optical quantum circuits and introduce a framework based on the ratio of sample variance to circuit variance. This ratio determines the number of circuit samples required to resolve local loss differences and gradients to proportional accuracy. We apply this framework to photon-number observables and identify both trainable and non-trainable regimes. Supported by analytic results and a numerically observed polynomial decay of the circuit variance, we find that fixed-order photon-number polynomials require only polynomially many samples as the system size grows, whereas high-order polynomials and observables based on output probabilities generally require exponentially many samples. Within the trainable regime, we further identify classes of observables in which quantum estimation achieves a polynomial speed-up over multiple classical methods. Within this family, neural network observables provide one practical construction that allow measurement outcomes to be efficiently processed into the desired polynomial. These results establish photonic variational quantum computing as a promising platform for near-term applications.
Alexander Makarovskiy, Adam J. Taylor, Zhenghao Li et al.· 1 citation
Deep generative models have become a leading approach for designing therapeutic molecules, yet efficiently exploring vast biomolecular sequence spaces remains difficult, particularly for targets with limited training data. The prior distribution that seeds a generative model shapes which regions of sequence space it explores, and recent work suggests that non-classical distributions sampled from quantum processors can serve as a structured alternative to the factorised Gaussian priors used by default. Whether such priors help on complex biological design tasks has been largely untested. Here we present what is, to our knowledge, the first end-to-end hybrid quantum-classical pipeline for de novo design of MHC class I-binding peptides, coupling a generative adversarial network (GAN) to latent vectors sampled from a real photonic quantum processor. Tested in silico across 131 HLA alleles, quantum-derived priors increased the yield of predicted strong binders, with the largest relative gains for understudied alleles where classical baselines perform worst. We selected three understudied alleles for further evaluation, finding that large gains coincided with broader sequence exploration at non-anchor positions while anchor specificity was preserved. On these three alleles, we validated the designs in vitro using peptide-MHC stability ELISAs, confirming that quantum-designed peptides are potent stabilisers of peptide-MHC class I complexes. These results establish structured, hardware-realisable non-classical priors as a useful inductive bias for generative peptide design, with direct relevance to personalised immunotherapies and vaccines.
E. S. Engdal, Jonathan Funk, O. Bacarreza et al.· bioRxiv· 0 citations